(Adapted from the applicant's abstract): The applicant's goal for this CAP award is to develop the multidisciplinary skills necessary to become expert in integrating complex genetic and clinical information in order to more fully characterize complex genetic neuropsychiatric disorders. Her developmental plans include focused research aimed at integrating clinical and genetic studies, as well as a program of course work, research seminars, and structured mentoring. Her research agenda is aimed at characterizing TS and its associated comorbitities from both clinical and genetic perspectives. Specifically, she will investigate potential correlations between genetic haplotypes and clinical variables such as symptom clusters and particular environmental variables in TS and TS spectrum disorders. This proposal has specific aims: 1) to expand the clinical data collected for the genetic study of TS for additional clinical and epidemiological investigations. a) to carefully characterize the phenomenology of TS by collecting specific information on a variety of clinical variables, and to evaluate the extent of comorbid disorders such as obsessive compulsive disorder (OCD) in the study sample. b) to evaluate the presence and extent of selected environmental variables (such as birth trauma) hypothesized to influence the course of TS; 2) to evaluate the relationship of high risk haplotypes and the presence or absence of specific environmental factors to specific clinical variables, such as presence or absence of comorbid disorders or symptom severity; 3) to identify and collect a sample of individuals with TS-spectrum disorders (such as chronic motor tic disorder), and to characterize these disorders with regard to associated comorbidities, associated environmental factors, and presence or absence of high risk TS aplotypes; and 4) to collect a sample of subjects with TS and TS-spectrum disorders from additional populations in order to formally assess relationships between genetic, environmental, and clinical factors identified in this study. The specific aims will be achieved by analyzing and correlating clinical and genetic information gathered from two genetically isolated populations, the Central Valley of Costa Rica and individuals of Ashkenazi Jewish descent in the United States. Clinical information will be collected in a systematic way, and will be expanded to include information on symptom types and severity, presence and severity of number of specific comorbidities, and presence of specific environmental factors postulated to be associated with TS. An additional study sample will be collected to investigate the role of these variables on TS spectrum disorders. Clinical and genetic information will be analyzed and correlations explored using a variety of statistical measures.